This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. i. Application of racemic protein crystallography to determine the X-ray structure of protein molecules, which are otherwise difficult to crystallize. This project involves the total chemical synthesis of native protein (i.e. L-protein) and its mirror image enantiomer (i.e. D-protein). Crystallization of a protein molecule from a racemic mixture (i.e. a solution containing equal proportions of L- and D- protein enantiomers) can lead to more facile formation of centrosymmetric crystals. The availability of centrosymmetric protein crystals in turn can facilitate ab initio structure solution by direct methods. We have recently demonstrated this racemic approach by producing the centrosymmeric protein crystals of Snowflee antifreeze protein and crambin from our laboratory. To explore the general utility of this approach we applied this method to other chemically synthesized proteins, which were difficult to crystallize with L-protein alone such as: antimicrobial micro-protein omwaprin, the largest ever known natural cyclotide palicourein, a hypothetical mycobacterium tuberculosis protein Rv1738. We also extended this method to obtaine crystals from a quasi-racemic mixture of D-crambin and topological analogue of L-crambin. ii. Elucidation of molecular details of HIV-1 protease catalysis, an important target in AIDS chemotherapy. Various chemical analogues were synthesized to perform 'dynamics/function'correlations in catalytic mechanism as well as totally artificial tunable catalytic apparatus was designed and incorporated.